Ethyl cyanoacetate → HCID 118101219, compound

HRID 708911Notes

Reaction equation

HRID 708911 reaction equation
Br[C:2]1[CH:20]=[CH:19][C:18]([N+:21]([O-:23])=[O:22])=[CH:17][C:3]=1[CH2:4][N:5]([CH3:16])[C:6](=[O:15])[O:7][CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.N1CCC[C@H]1C(O)=O.C(=O)([O-])[O-].[Cs+].[Cs+].[C:38]([CH2:40][C:41]([O:43][CH2:44][CH3:45])=[O:42])#[N:39]>CS(C)=O.[Cu]I>[CH2:8]([O:7][C:6]([N:5]([CH2:4][C:3]1[CH:17]=[C:18]([N+:21]([O-:23])=[O:22])[CH:19]=[CH:20][C:2]=1[CH:40]([C:38]#[N:39])[C:41]([O:43][CH2:44][CH3:45])=[O:42])[CH3:16])=[O:15])[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1

Participants

7

Reactant 4

HCID 7764Ethyl cyanoacetateHCID 10796Cesium carbonateHCID 145742L-ProlineHCID 66744764HCID 66744764, compound

Product 1

HCID 118101219HCID 118101219, compoundYield 80.2%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
50 °C

Procedure

36A (3.000 g, 7.91 mmol), copper(I) iodide (0.301 g, 1.582 mmol), L-proline (0.364 g, 3.16 mmol) and cesium carbonate (5.16 g, 15.82 mmol) were mixed in a pressure vial and degassed (3× vacuum/Ar). Then, a solution of ethyl 2-cyanoacetate (1.059 mL, 9.89 mmol) in DMSO (10 mL) was added, the reaction mixture was degassed again and stirred at 50° C. for 3 days. The cooled reaction mixture was partitioned between EtOAc (100 mL) and sat. NH4Cl (100 mL). The organic layer was washed with brine (2×50 mL) and dried (Na2SO4). EtOAc was removed under reduced pressure and the residue was purified by flash chromatography to give 36B (2.609 g, 6.34 mmol, 80% yield) as a yellowish syrup. MS (ESI) m/z: 412.2 [M+1]+. 1H NMR: (400 MHz, CDCl3) δ ppm 8.24 (1H, d, J=8.03 Hz), 8.14 (1H, br. s.), 7.79 (1H, d, J=8.53 Hz), 7.29-7.43 (5H, m), 5.67 (1H, br. s.), 5.18 (2H, s), 4.50-4.86 (2H, m), 4.14-4.29 (2H, m), 2.90 (3H, s), 1.27 (3H, t, J=7.15 Hz).

Workup

  1. customdegassed (3× vacuum/Ar)
  2. customthe reaction mixture was degassed again
  3. customThe cooled reaction mixture
  4. customwas partitioned between EtOAc (100 mL) and sat. NH4Cl (100 mL)
  5. washThe organic layer was washed with brine (2×50 mL)
  6. dry with materialdried (Na2SO4)
  7. customEtOAc was removed under reduced pressure
  8. customthe residue was purified by flash chromatography

Sources & evidence

ORD record
ord-aa027033769c45b6a7f4f2e2cd76719b
Source dataset
uspto-grants-2015_11
Patent number
US09174974B2

Reaction notes

Loading…